Parenteral lethality

Parenteral lethality was determined by injecting rabbits of mixed sexes intraperitoneally with 31.6, 63, 126, 252, and 500 /xg/kg of 2,3,7,8-TCDD as a 0.01% corn oil suspension control rabbits were injected with corn oil. The rabbits were housed in individual holding cages and were observed for signs of toxicity for four weeks. The LDso s were calculated by the Weil modification of the Thompson method 14, 15) or by the Litchfield and Wilcoxon method (9). The acute lethality studies were terminated when it was evident that the survivors were not showing signs of toxicity. 

Canine parvovirus (CPV) VP2 epitope Epitope display on cowpea mosaic virus in cowpea leaf Immunogenic in mice when delivered parenter-ally or nasally. Dogs developed 3L17- and VP2-specific IgG sera neutralized CPV in vitro. Protective against lethal challenge in dogs immunized parenterally. 76, 77... 

Rabbit hemorrhagic disease vims VP60 epitope Epitope display on plum pox potyvirus in tobacco leaf Rabbits developed specific antibodies that showed neutralizing activity. Immunogenic when delivered to mice parenterally immunogenic in rabbits when delivered parenterally. Rabbits immunized parenterally survived lethal challenge. 78, 84... 

Rabies virus glycoprotein (G)and nucleo-protein (N) Alfala mosaic virus and tobacco mosaic vims in tobacco and spinach leaf Elicited specific virus-neutralizing antibodies in mice. Immunogenic in mice when delivered orally and parenterally immunogenic in humans when delivered orally. Moderately protective against lethal challenge infection in mice. 16, 71... 

Nickel salts administered by intravenous or subcutaneous injection are comparatively toxic. For all routes of parenteral administration, the LD50 (lethal dose to 50% of the sample) range for injected nickel salts is 6 mg Ni/kg BW for dogs given nickel oxide intravenously to 600 mg Ni/kg BW for mice given nickel disodium F.DTA intraperitoneally (Nielsen 1977). 

Amide-type agents include articaine, lidocaine, bupivacaine, prilocaine, mepivacain and ropiva-caine. These are metabolized in the liver by microsomal enzymes with amidase activity. The amide group is preferred for parenteral and local use. If by accident rapidly administered intravascularly these agents, especially bupivacaine but also lidocaine, can produce serious and potentially lethal adverse effects including convulsions and cardiac arrest. They can more easily accumulate after multiple administrations. Intravenous lidocaine is sometimes used for regional anesthesia, for infiltration procedures, for the induction of nerve blockade and for epidural anesthesia. However, it is also used as an antiarrhythmic. Bupivacaine is a long-acting local anesthetic used for peripheral nerve blocks and epidural anesthesia. 

In endemic areas malaria should always be considered and, if possible, checked by blood film analysis otherwise empiric antimalarial treatment may be indicated (see section on malaria). Empiric treatment should further cover the spectrum of bacterial agents likely to cause septic infections in the particular patient. The potentially fatal course of septic disease requires an antibiotic regimen that is rapidly lethal for the causative agent, and preferably attains adequate levels at the site of infection quickly. Therefore, treatment regimens usually include a combination of two (sometimes three) antibiotics that are given by a parenteral route (intramuscularly or preferably by intravenous infusion). 

No studies were located regarding acute lethality in humans following parenteral administration of radium isotopes. Early uses of radium-226 by physicians (usually as a treatment for arthritis)... 

Human parenteral toxicity for abrin is approximately 0.1-1 Jig/kg (Romano et al, 2007). However, based on clinical trials on abrin-immunotoxin use for cancer treatment, the human minimum lethal dose by intravenous injection was estimated to be >0.3 Jig/kg without occurrence of serious adverse effects (Gill, 1982). 

While scant literature is available on persistence and distribution after inhalation exposure, several studies have evaluated the systemic behavior of parenterally administered toxins. One group investigated toxin persistence in serum and tissue distribution in white mice following intravenous (IV) administration of 1,000 lethal doses of S-labeled type B toxin (Pak and Bulatova, 1962). Mice were sacrificed at 20, 60, and 150 min after toxin administration, and blood and tissues were harvested for toxin distribution analysis. These mice showed symptoms of severe intoxication, including atypical breathing patterns and paralysis, at 150 min post-exposure. Toxin levels (as determined by... 

Somewhat slower kinetics for toxin clearance from the circulation were observed in dogs following parenteral [IV, IP, or intramuscular (IM)] exposure to type A toxin (House et al, 1964). Serum toxin persistence was evaluated in mongrel dogs receiving 8,000 to 10,000 mouse units/kg of type A toxin. Peak serum toxin levels were detected 5 h after IP administration (13% of injected dose), 12 h after IM administration (9% of injected dose), and within only 3 min after IV administration (79% of injected dose) (House et al., 1964). The relative clearance kinetics were slower after IM and IP exposure than for IV administration, as serum toxin levels were identical 22 h after injection via all three rounds (approximately 6% of injected dose). Some serum toxin activity could be detected by the mouse lethality assay for 2 to 4 days after parenteral administration. Serum toxin patterns were also evaluated in rhesus monkeys following IV administration of type A toxin (Stookey et al., 1965). Serum toxin levels dropped by about 50% of maximum within 16 to 24 h after IV injection, and previous exposure did not affect toxin clearance rates after the administration of subsequent doses. 

Transdermal exposure to ricin is not serious, since it is not well absorbed through the skin. Oral exposure, for example by ingestion of castor beans, can cause severe gastroenteritis, gastrointestinal hemorrhage, and death due to circulatory collapse. Parenteral injection of ricin is rapidly fatal, as is aerosol exposure the lethal dose by these routes is 5-10 micrograms/kg (8). 

However, both toxins have equal lethal potencies when injected parenterally (Arnon et al., 1984 Lyerly et al., 1985) about 50 ng of either toxin injected intraperitoneally is sufficient to kill a 25 g mouse (Lyerly etal., 1986). Furthermore, in the presence of sublethal amounts of ToxA, also ToxB is lethal when given by the intragastric route (Lyerly et al., 1985). Indeed both toxins seem to play a role in the disease, according to vaccination studies with toxoids (Libby et al., 1982). This is supported by a recent study on human colonic tissue (see section 12.5.1). 

MCA poisoning by ingestion, inhalation or exposure of more than 5% of the body surface area is frequently lethal. The symptoms of poisoning are not immediate they can appear between 1 and 4 hours after exposure. The non-corrosive sodium salt does not penetrate the skin and is not toxic by skin contact (unlike MCA, which passes through the skin very easily). It is, on the other hand, highly toxic by the oral route. There are no data available on the parenteral administration of MCA in humans. In laboratory animals. 

While the results in animal studies indicate that exposure to high doses of PAHs is lethal, the majority of the data are from parenteral exposure. This route is not applicable to exposure routes humans may expect to encounter, so the relevance of these findings to public health is not known. Parenteral administration bypasses the first-pass effect in the liver that occurs following oral exposure (PAHs may be expected to be ultimately biotransformed to inactive metabolites more quickly in the liver than in other tissues). However, because death has been observed in animals following oral exposure as well, it can be assumed that acute exposure to high enough doses of the PAHs can be lethal. 

Comparison of the Parenteral Lethality of Ricin and Related Toxins in Laboratory Mice... 

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